A Cohesin Subunit Variant Identified from a Peripheral Sclerocornea Pedigree
| Autor: | Vishal Jhanji, Chi Pui Pang, Bi Ning Zhang, Li Jia Chen, Pancy O. S. Tam, Yu Liu, Tommy C Y Chan, Wai Kit Chu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Clinical Biochemistry Cell Cycle Proteins Corneal Diseases Pathogenesis Cornea 0302 clinical medicine Lymphocytes Child Cells Cultured Aged 80 and over lcsh:R5-920 General Medicine Middle Aged Prognosis Peripheral Pedigree DNA-Binding Proteins medicine.anatomical_structure 030220 oncology & carcinogenesis Female Ploidy lcsh:Medicine (General) Research Article Adult medicine.medical_specialty Article Subject Adolescent Biology 03 medical and health sciences Young Adult Ophthalmology Genetics medicine Humans Sclerocornea Molecular Biology Mitosis Aged Retrospective Studies Cohesin Biochemistry (medical) medicine.disease Protein Subunits 030104 developmental biology Mutation sense organs Biomarkers Congenital disorder Follow-Up Studies |
| Zdroj: | Disease Markers Disease Markers, Vol 2019 (2019) |
| ISSN: | 1875-8630 0278-0240 |
| Popis: | Background. Sclerocornea is a rare congenital disorder characterized with the opacification of the cornea. Here, we report a nonconsanguineous Chinese family with multiple peripheral sclerocornea patients spanning across three generations inherited in an autosomal dominant manner. Methods. This is a retrospective case series of a peripheral sclerocornea pedigree. Comprehensive ophthalmic examinations were conducted and assessed on 14 pedigree members. Whole-exome sequencing was used to identify the genetic alterations in the affected pedigree members. Lymphoblastoid cell lines (LCLs) were established using blood samples from the family members. Functional tests were performed with these cell lines. Results. Six affected and eight unaffected members of a family with peripheral sclerocornea were examined. All affected individuals showed features of scleralization over the peripheral cornea of both eyes. Mean horizontal and vertical corneal diameter were found significantly decreased in the affected members. Significant differences were also observed on the mean apex pachymetry between affected and unaffected subjects. These ophthalmic parameters did not resemble that of cornea plana. A RAD21C1348T variant was identified by whole-exome sequencing. Although this variant causes RAD21 R450C substitution at the separase cleavage site, cells from peripheral sclerocornea family members had no mitosis and ploidy defects. Conclusion. We report a family of peripheral sclerocornea with no association with cornea plana. A RAD21 variant was found cosegregating with peripheral sclerocornea. Our results suggest that RAD21 functions, other than its cell cycle and chromosome segregation regulations, could underline the pathogenesis of peripheral sclerocornea. |
| Databáze: | OpenAIRE |
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